Post-hypoxic constriction of retinal arterioles is impaired during nitric oxide and cyclo-oxygenase inhibition and in diabetic patients without retinopathy

Abstract

Occlusion of retinal vessels leads to retinal ischaemia and hypoxia, which induces vasodilatation in adjacent retinal areas in order to normalize retinal oxygenation. Previous studies have shown that NO and COX products are involved in hypoxia-induced dilatation of retinal arterioles in vitro and in vivo, and that this response is disturbed in patients with diabetes mellitus. However, it is unknown to what extent post-hypoxic recovery of the diameter of retinal arterioles depends on NO and COX products in normal persons and in diabetic patients. The Dynamic Vessel Analyzer (DVA) was used to study the post-hypoxic diameter changes of larger retinal vessels in 20 normal persons, 20 diabetic patients without diabetic retinopathy, and in 18 patients with diabetic maculopathy before and after inhibition of the synthesis of nitric oxide and COX products. In normal persons, the arterioles had re-constricted (p > 0.99) 2 minutes after termination of hypoxia in the absence of antagonists, but not after treatment with L-NMMA and diclofenac (p < 0.01 for all comparisons). In diabetic patients without retinopathy, the arterioles showed no diameter changes after termination of hypoxia during any of the interventions. In patients with diabetic maculopathy hypoxia had not dilated retinal arterioles (p > 0.1 for all comparisons) to allow the study of re-constriction. In all groups, the dilatation of venules remained significantly increased during the post-hypoxic observation period, both in the absence and in the presence of L-NMMA and diclofenac.Post-hypoxic constriction of retinal arterioles depends on NO and COX products, and is impaired in diabetic patients before the development of retinopathy. This disturbance may contribute to the development of diabetic retinopathy, and should be the target of future interventional studies aimed at preventing and treating the disease.ClinicalTrials.gov identifier: NCT01689090.

Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy

“…The diameter changes during isometric exercise and flicker stimulation were also lower in diabetic patients than in normal persons, which confirms previous findings [31][32][33], but the fact that the difference was only significant for flicker-induced dilatation during carbon dioxide breathing within the first 24 h after onset of dorzolamide treatment is suggestive. It is possible that the effect may be related to induction of carbonic anhydrase [34], but the finding requires further substantiation.…”

The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene‐related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro

“…This points to inducible NO as a final common mediator for relaxation of retinal arterioles secondary to a variety of stimuli. It has been proposed that disturbances in the site of metabolism of NO may contribute to the development of retinal vascular disease (Schmetterer & Polak, 2001) which is supported by several clinical intervention studies (Pemp et al, 2009; Petersen & Bek, 2016, 2017).…”

Comparative study of microvascular function: Forearm blood flow versus dynamic retinal vessel analysis

“…Subsequently, the commercially available dynamic vessel analyser system was launched (Garhofer et al., 2010; Nagel et al., 2001; Polak et al., 2002) and a decrease of flickering light‐induced dilation of the retinal vasculature has been reported in several conditions that were at least partly associated with endothelial dysfunction like impaired glucose tolerance, diabetic retinopathy, untreated hypertension, hyperlipidaemia and obesity (Kotliar et al., 2011; Lim et al., 2014; Nagel et al., 2004; Patel et al., 2012; Reimann et al., 2009). Instead of flickering light, systemic hypoxia, systemic N G ‐monomethyl‐L‐arginine (L‐NMMA) and hyperglycaemic clamp were used to instantly assess retinal vessel diameter reactions (Bursell et al., 1996; Delles et al., 2004; Petersen & Bek, 2017). However, these methods are very complex for routine clinical use and are also problematic for cardiovascular high‐risk patients.…”